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Current Protein & Peptide
Science
ISSN: 1389-2042
Current Protein and Peptide
Science
Volume 7, Number 2, April 2006
Contents
Recent Advances in Azo Dye Degrading Enzyme Research Pp.
101-111
Huizhong Chen
[Abstract]
Biochemical and Molecular Basis of Insulin Resistance
Pp. 113-121
Chiranjib Chakraborty
[Abstract]
Structure and Function of the Epstein-Barr Virus
Transcription Factor, EBNA 3C Pp. 123-136
Michelle J. West
[Abstract]
Advances in HTLV-1 Peptide Vaccines and Therapeutics
Pp. 137-145
Marcus P. Lynch and Pravin T.P. Kaumaya
[Abstract]
Transcriptome Analyses of Human Genes and Applications
for Proteome Analyses Pp. 147-163
Yutaka Suzuki and Sumio Sugano
[Abstract]
Recombinant Antibodies in Cancer Therapy
Pp. 165-170
M.S. Nayeem and Rizwan H. Khan
[Abstract]
Cytokine-Regulated Protein Degradation by the Ubiquitination
System Pp. 171-177
Kwang-Hyun Baek
[Abstract]
Abstracts
[Back to top]
Recent Advances in Azo Dye Degrading Enzyme Research
Huizhong Chen
Azo dyes, which are characterized by one or more azo bonds,
are a predominant class of colorants used in tattooing, cosmetics,
foods, and consumer products. These dyes are mainly metabolized
by bacteria to colorless aromatic amines, some of which are
carcinogenic, by azoreductases that catalyze a NAD(P)H-dependent
reduction. The resulting amines are further degraded aerobically
by bacteria. Some bacteria have the ability to degrade azo
dyes both aerobically and anaerobically. Plant-degrading white
rot fungi can break down azo dyes by utilizing a number of
oxidases and peroxidases as well. In yeast, a ferric reductase
system participates in the extracellular reduction of azo
dyes. Recently, two types of azoreductases have been discovered
in bacteria. The first class of azoreductases is monomeric
flavin-free enzymes containing a putative NAD(P)H binding
motif at their N-termini; the second class is polymeric flavin
dependent enzymes which are studied more extensively. Azoreductases
from bacteria represent novel families of enzymes with little
similarity to other reductases. Dissociation and reconstitution
of the flavin dependent azoreductases demonstrate that the
non-covalent bound flavin prosthetic group is required for
the enzymatic functions. In this review, structures and carcino-genicity
of azo colorants, protein structure, enzymatic function, and
substrate specificity, as well as application of the azo dyes
and azoreductases will be discussed.
[Back to top]
Biochemical and Molecular Basis of Insulin Resistance
Chiranjib Chakraborty
Insulin-resistance is a major problem associated with diabetes
and that is increasing rapidly worldwide. Insulin is a peptide
hormone secreted by the β-cells
of the pancreatic islets of Langerhans in response to increased
circulating levels of glucose and amino acids and it is essential
for appropriate tissue development, growth, and maintenance
of whole-body glucose homeostasis by regulating carbohydrate,
lipid and protein metabolism. Insulin resistance is a defect
in signal transduction. The signaling mechanisms involved
in the various biologic responses to insulin remain somewhat
elusive. This review focuses on the structure and activity
of insulin receptor, inheritance of insulin resistance, insulin
receptor and alleles, enzyme activity in insulin resistance,
insulin receptor in phosphorylation and relating substrate.
We have discussed insulin receptor substrate-family (IRS)
related to insulin resistance, detail downstream signaling
effects, GLUT4 vesicle translocation and related events, cytokine-mediated
insulin resistance, and feedback control mechanisms. This
review also focuses on insulin resistance in obesity-linked
metabolic syndrome, insulin resistance related to plasma membrane
disturbances and insulin resistance for exercise and cellular
integrity. Finally, we can conclude that insulin resistance
is really a complex phenomenon in which several genetic defects
combine with environmental stresses.
[Back to top]
Structure and Function of the Epstein-Barr Virus Transcription
Factor, EBNA 3C
Michelle J. West
EBNA 3C is one of only nine proteins expressed by the tumourigenic
γ-herpesvirus
Epstein-Barr virus (EBV) during the infection and immortalization
of human B lymphocytes. In fact, the expression of EBNA 3C
has been shown to be essential for the B-cell transformation
process to take place. The mechanism by which EBNA 3C contributes
to viral pathogenicity has therefore been the subject of intensive
research over many years. The first clues on the function
of EBNA 3C came from analysis of the primary amino acid sequence
of EBNA 3C which identified a number of domains commonly found
in transcriptional regulatory proteins. These domains include
a proline-rich and a glutamine-proline-rich domain and a putative
bZIP domain located in the N-terminus of the protein. EBNA
3C has subsequently been shown to function as a regulator
of both viral and cellular transcription and to have potent
effects on normal cell-cycle regulatory pathways. This review
will discuss our current knowledge of the functions of EBNA
3C, the roles played by the different domains of EBNA 3C in
these functions, and summarize some recent work from our laboratory
that provides the first structural and functional analysis
of the putative bZIP domain of EBNA 3C.
[Back to top]
Advances in HTLV-1 Peptide Vaccines and Therapeutics
Marcus P. Lynch and Pravin T.P. Kaumaya
In the past two decades a large initiative has been put
forth to understand the biological and pathogenic properties
of the human T-cell lymphotropic virus type 1 (HTLV-1); this
has ultimately led to the development of various experimental
vaccination and therapeutic strategies to combat HTLV-1 infection.
The focus of this work is to outline key targets for the design
of therapeutics for HTLV-1, such as fusion mediated by the
envelope glycoprotein, and to discuss reports of novel vaccines
or therapeutics. These strategies include peptide, recombinant
protein, DNA, and viral vectors. The final focus of this review
is to acquaint the reader with vaccine approaches developed
in our laboratory over the last decade. These strategies include
the development of envelope glycoprotein derived B-cell epitopes
for the induction of neutralizing antibodies, as well as a
strategy to generate a multivalent cytotoxic T-lymphocyte
(CTL) response against the HTLV-1 Tax antigen.
[Back to top]
Transcriptome Analyses of Human Genes and Applications
for Proteome Analyses
Yutaka Suzuki and Sumio Sugano
By utilizing recently developed full-length cDNA technologies,
large-scale cDNA sequencing was carried out by several cDNA
projects. Now full-length cDNA resources cover the major part
of the protein-coding human genes. Comprehensive analyses
of the collected full-length cDNA data revealed not only the
complete sequences of thousands of novel gene transcripts
but also novel alternatively spliced isoforms of hitherto
identified genes. However, it was not as easy as expected
to deduce their encoded amino acid sequences based solely
on the full-length cDNA sequences. It was neither always the
case that the longest open reading frame corresponded to the
real protein coding region nor that the first ATG was the
translation initiator codon. Also, proteome-wide mass-spectrometry
analysis has shown that there is an unexpectedly large population
of small proteins, encoded by so-called upstream open reading
frames, within the cell. Since sound manual annotations by
experts were still indispensable to address these problems,
an international meeting to make transcriptome-wide functional
annotations of cDNAs was held, namely the H-invitational.
In this meeting, functional annotations were made both manually
and computationally for most of the pre-existing full-length
cDNAs collected from world-wide cDNA projects. The achieved
integrated information for each of the cDNAs was published
as a database. It was also shown that the full-length cDNA
data were useful for identifying alternative splicing variants,
exact transcriptional start sites of the mRNAs and the adjacent
promoter regions. Rapidly accumulating genome data as well
as versatile use of the transcriptome information will shortly
lay a firm foundation for proteome-level understanding of
human gene networks.
[Back to top]
Recombinant Antibodies in Cancer Therapy
M.S. Nayeem and Rizwan H. Khan
The application of recombinant immunotoxin and radioimmunoconjugate
in Cancer therapy has revived the “magic bullet”
concept predicted a century ago. Many of the recombinant antibodies
have received FDA approval for various indication of cancer
in recent years and numerous others are in clinical trials.
[Back to top]
Cytokine-Regulated Protein Degradation by the Ubiquitination
System
Kwang-Hyun Baek
The ubiquitin-mediated protein degradation pathway exerts
a wide spectrum of effects and modulates a variety of biological
processes including cell cycle progression, transcriptional
regulation, signal transduction, antigen presentation, apoptosis
(or programmed cell death), oncogenesis, preimplantation,
and DNA repair. Recently, the importance of deubiquitination
mechanism has been emerged as an essential regulatory step
to control these cellular mechanisms for homeostasis. Even
though a number of deubiquitinating enzymes have recently
been isolated, relatively little is known about their substrates
and biological functions. Identified from yeast to human,
deubiquitinating (DUB) enzymes are classified into the ubiquitin
C-terminal hydrolase (UCH), the ubiquitin-specific processing
proteases (UBP or USP), Jab1/Pad1/MPN domain containing metallo-enzymes
(JAMM), Otu domain ubiquitin-aldehyde binding proteins (OTU),
and Ataxin-3/Josephin domain containing proteins (Ataxin-3/Josephin).
Several members of a novel DUB subfamily in-duced by cytokines
in murine lymphocytes have recently been identified. In addition,
human DUB enzyme DUB-3, highly homologous to USP17 and induced
by cytokines interleukin (IL)-4 and IL-6, has been recently
isolated and showed that it has significant homology to the
known murine DUB subfamily members. Interestingly, both murine
DUB and human USP17 subfamily members are
localized and clustered on murine chromosome 7 and on human
chromosomes 4 and 8, respectively. This review introduces
the reader to provide a great understanding of cytokine-inducible
DUB en-zymes in both mouse and human, and new insights into
DUB subfamily members.
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